14,451 research outputs found

    Multilevel functional principal component analysis

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    The Sleep Heart Health Study (SHHS) is a comprehensive landmark study of sleep and its impacts on health outcomes. A primary metric of the SHHS is the in-home polysomnogram, which includes two electroencephalographic (EEG) channels for each subject, at two visits. The volume and importance of this data presents enormous challenges for analysis. To address these challenges, we introduce multilevel functional principal component analysis (MFPCA), a novel statistical methodology designed to extract core intra- and inter-subject geometric components of multilevel functional data. Though motivated by the SHHS, the proposed methodology is generally applicable, with potential relevance to many modern scientific studies of hierarchical or longitudinal functional outcomes. Notably, using MFPCA, we identify and quantify associations between EEG activity during sleep and adverse cardiovascular outcomes.Comment: Published in at http://dx.doi.org/10.1214/08-AOAS206 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

    The Y-box factor ZONAB/DbpA associates with GEF-H1/Lfc and mediates Rho-stimulated transcription

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    Epithelial tight junctions recruit different types of signalling proteins that regulate cell proliferation and differentiation. Little is known about how such proteins interact functionally and biochemically with each other. Here, we focus on the Y-box transcription factor ZONAB (zonula occludens 1-associated nucleic-acid-binding protein)/DbpA (DNA-binding protein A) and the Rho GTPase activator guanine nucleotide exchange factor (GEF)-H1/Lbc's first cousin, which are two tight-junction-associated signalling proteins that regulate proliferation. Our data show that the two proteins interact and that ZONAB activity is Rho-dependent. Overexpression of GEF-H1 induces accumulation of ZONAB in the nucleus and activates transcription. Microtubule-affinity regulating kinase/partition-defective-1, another type of GEF-H1-associated signalling protein, remains in the cytoplasm and partially co-localizes with the exchange factor. GEF-H1 and ZONAB are required for expression of endogenous cyclin D1, a crucial RhoA signalling target gene, and GEF-H1-stimulated cyclin D1 promoter activity requires ZONAB. Our data thus indicate that GEF-H1 and ZONAB form a signalling module that mediates Rho-regulated cyclin D1 promoter activation and expression

    Platelet-derived transforming growth factor-β1 promotes keratinocyte proliferation in cutaneous wound healing.

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    Platelets are a recognised potent source of transforming growth factor-β1 (TGFβ1), a cytokine known to promote wound healing and regeneration by stimulating dermal fibroblast proliferation and extracellular matrix deposition. Platelet lysate has been advocated as a novel personalised therapeutic to treat persistent wounds, although the precise platelet-derived growth factors responsible for these beneficial effects have not been fully elucidated. The aim of this study was to investigate the specific role of platelet-derived TGFβ1 in cutaneous wound healing. Using a transgenic mouse with a targeted deletion of TGFβ1 in megakaryocytes and platelets (TGFβ1fl/fl .PF4-Cre), we show for the first time that platelet-derived TGFβ1 contributes to epidermal and dermal thickening and cellular turnover after excisional skin wounding. In vitro studies demonstrate that human dermal fibroblasts stimulated with platelet lysate containing high levels of platelet-derived TGFβ1 did not exhibit enhanced collagen deposition or proliferation, suggesting that platelet-derived TGFβ1 is not a key promoter of these wound healing processes. Interestingly, human keratinocytes displayed enhanced TGFβ1-driven proliferation in response to platelet lysate, reminiscent of our in vivo findings. In summary, our novel findings define and emphasise an important role of platelet-derived TGFβ1 in epidermal remodelling and regeneration processes during cutaneous wound healing

    Structural relaxation in a system of dumbbell molecules

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    The interaction-site-density-fluctuation correlators, the dipole-relaxation functions, and the mean-squared displacements of a system of symmetric dumbbells of fused hard spheres are calculated for two representative elongations of the molecules within the mode-coupling theory for the evolution of glassy dynamics. For large elongations, universal relaxation laws for states near the glass transition are valid for parameters and time intervals similar to the ones found for the hard-sphere system. Rotation-translation coupling leads to an enlarged crossover interval for the mean-squared displacement of the constituent atoms between the end of the von Schweidler regime and the beginning of the diffusion process. For small elongations, the superposition principle for the reorientational α\alpha-process is violated for parameters and time intervals of interest for data analysis, and there is a strong breaking of the coupling of the α\alpha-relaxation scale for the diffusion process with that for representative density fluctuations and for dipole reorientations.Comment: 15 pages, 14 figures, Phys. Rev. E in pres

    Implementing Inquiry-based Learning and Examining the Effects in Junior College Probability Lessons

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    This study examined how Year 12 students use their inquiry skills in solving conditional probability questions by means of Inquiry-Based Learning application. The participants consisted of 66 students of similar academic abilities in Mathematics, selected from three classes, along with their respective teachers. Observational rubric and lesson observation checklist were used as the data collection instruments. The results obtained were analyzed and then quantitatively reported. Findings from the observational rubric revealed that Year 12 students were able to understand most of the questions during the activity, but they only select and use one previously learned method to solve the questions during the activity. In addition, these students rarely seek and asked probing questions during the activity. They only used words, diagrams and numbers to interpret the solutions to the questions and make connections between them but with few mistakes detected.DOI: http://dx.doi.org/10.22342/jme.8.2.3964.157-16

    Mode-coupling theory for structural and conformational dynamics of polymer melts

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    A mode-coupling theory for dense polymeric systems is developed which unifyingly incorporates the segmental cage effect relevant for structural slowing down and polymer chain conformational degrees of freedom. An ideal glass transition of polymer melts is predicted which becomes molecular-weight independent for large molecules. The theory provides a microscopic justification for the use of the Rouse theory in polymer melts, and the results for Rouse-mode correlators and mean-squared displacements are in good agreement with computer simulation results.Comment: 4 pages, 3 figures, Phys. Rev. Lett. in pres
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